A frontal pole cDNA library from the rhesus monkey brain was shown to have 6 cDNA clones which were differentially expressed as compared with primary sensory cortices. Three of these clones showed homology to the mitochondrial DNA encoded genes, cytochrome oxidase subunits I, II and III, reflecting greater neuropil (synapses and dendrites) and mitochondrial density in association as compared with primary cortices. Such differences in gene expression may be related to selective vulnerability of association than of primary cortical regions in Alzheimer's disease in humans. Mouse trisomy 16 (Ts16), an animal model for Down syndrome in humans, is a lethal chromosomal abnormality leading to fetal death. However, Ts16 hippocampal and neocortical brain regions were successfully transplanted into brains of normal adult mouse hosts. Alzheimer's disease neuropathology, suggesting that increased expression of the genes comparable to those on human chromosome 21 is insufficient to cause Alzheimer type degeneration in the mouse. GRANT=Z01AG00140 Young adult Down syndrome subjects had elevated levels of cerebrospinal fluid choline, but acetylcholinesterase activity and somatostatin and neuropeptide Y concentrations did not differ from control values in either young or old Down patients. Analysis of lumbar cerebrospinal fluid fractions in healthy young and old subjects indicated no anterior-posterior gradients for somatostatin and neuropeptide Y, but higher acetylcholinesterase in caudal as compared to rostral fractions in younger subjects, indicative of sources for this enzyme from the spinal cord. Soluble interleukin-2 receptor levels in cerebrospinal fluid were not elevated in patients with Alzheimer's disease, suggesting that this disease is not associated with lymphocyte activation in the central nervous system.